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Integrated plasma and urine metabolomics coupled with HPLC/QTOF-MS and chemometric analysis on potential biomarkers in liver injury and hepatoprotective effects of Er-Zhi-Wan

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Abstract

Metabolomics techniques are the comprehensive assessment of endogenous metabolites in a biological system and may provide additional insight into the molecular mechanisms. Er-Zhi-Wan (EZW) is a traditional Chinese medicine formula, which contains Fructus Ligustri Lucidi (FLL) and Herba Ecliptae (HE). EZW is widely used to prevent and treat various liver injuries through the nourishment of the liver. However, the precise molecular mechanism of hepatoprotective effects has not been comprehensively explored. Here, an integrated metabolomics strategy was designed to assess the effects and possible mechanisms of EZW against carbon tetrachloride-induced liver injury, a commonly used model of both acute and chronic liver intoxication. High-performance chromatography/quadrupole time-of-flight mass spectrometry (HPLC/QTOF-MS) combined with chemometric approaches including principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) were used to discover differentiating metabolites in metabolomics data of rat plasma and urine. Results indicate six differentiating metabolites, tryptophan, sphinganine, tetrahydrocorticosterone, pipecolic acid, l-2-amino-3-oxobutanoic acid and phosphoribosyl pyrophosphate, in the positive mode. Functional pathway analysis revealed that the alterations in these metabolites were associated with tryptophan metabolism, sphingolipid metabolism, steroid hormone biosynthesis, lysine degradation, glycine, serine and threonine metabolism, and pentose phosphate pathway. Of note, EZW has a potential pharmacological effect, which might be through regulating multiple perturbed pathways to the normal state. Our findings also showed that the robust integrated metabolomics techniques are promising for identifying more biomarkers and pathways and helping to clarify the function mechanisms of traditional Chinese medicine.

Overview of the integrated metabolomics strategy

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Acknowledgments

This work was financially supported by National Natural Science Foundation of China (Grant No. 81001599, 81173547, and 81373972) and A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).

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Authors and Affiliations

  1. College of Pharmacy, Nanjing University of Chinese Medicine, 210023, Nanjing, Jiangsu, China

    Weifeng Yao, Beihua Bao, Li Zhang, Anwei Ding & Wei Li

  2. Northwest Metabolomics Research Center, Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA, 98109, USA

    Weifeng Yao, Haiwei Gu, Jiangjiang Zhu & Gregory Barding

  3. Jiangsu Engineering Laboratory for Research and Industrialization of Empirical Formulae, Nanjing University of Chinese Medicine, 210023, Nanjing, Jiangsu, China

    Haibo Cheng

  4. Jiangsu Key Laboratory for Traditional Chinese Medicine Formulae Research, Nanjing University of Chinese Medicine, 210023, Nanjing, Jiangsu, China

    Beihua Bao, Li Zhang & Anwei Ding

  5. Jiangxi Key Laboratory for Mass Spectrometry and Instrumentation, East China Institute of Technology, 330013, Nanchang, Jiangxi, China

    Haiwei Gu

  6. Department of Chemistry and Biochemistry, California State Polytechnic University, Pomona, CA, 91768, USA

    Gregory Barding

Authors
  1. Weifeng Yao
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  2. Haiwei Gu
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  5. Haibo Cheng
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  7. Li Zhang
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  9. Wei Li
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Correspondence to Li Zhang or Anwei Ding.

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Yao, W., Gu, H., Zhu, J. et al. Integrated plasma and urine metabolomics coupled with HPLC/QTOF-MS and chemometric analysis on potential biomarkers in liver injury and hepatoprotective effects of Er-Zhi-Wan. Anal Bioanal Chem 406, 7367–7378 (2014). https://doi.org/10.1007/s00216-014-8169-x

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  • DOI: https://doi.org/10.1007/s00216-014-8169-x

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